Objective To investigate the effect of circulating tumor cells （CTCS） combined with ductoscopy imaging system to improve the diagnostic efficiency of malignant lesions in patients with bloody nipple discharge. Methods Clinical data of 120 patients with bloody nipple discharge in our hospital from September 2019 to June 2023 were retrospectively analyzed， and all patients underwent peripheral blood CTC and ductoscopy. With pathological results as the gold standard， the diagnostic efficacy of CTC and ductoscopy in the diagnosis of malignant lesions in patients with bloody nipple discharge alone and in combination is evaluated. Results Pathological results of 120 patients showed benign lesions in 88 cases and malignant lesions in 32 cases. The count of CTCS in malignant lesion group was 1（0.5， 2.5）cells/3.2 mL， higher than that in benign lesion group 0（0， 1）cells/3.2 mL（P < 0.001）. ROC curve showed that the best cutoff value of CTC count for the diagnosis of malignant lesions in patients with bloody nipple discharge was 2 cells /3.2 mL. A total of 103 benign lesions and 17 malignant lesions were detected. 77 benign lesions and 43 malignant lesions were detected by ductoscopy imaging system. Using pathological results as the gold standard， the diagnostic sensitivity， specificity， accuracy， positive predictive value and negative predictive value of CTC for malignant lesions in patients with bloody nipple discharge were 46.88%， 97.73%， 84.17%， 88.24% and 83.50%， respectively. 84.38%， 81.82%， 82.50%， 62.79%， 93.51% for ductoscopy， and 96.88%， 81.82%， 85.83%， 65.96%， 98.63% for CTC combined with ductoscopy. Conclusion The diagnosis of malignant lesions in patients with bloody nipple discharge by CTC combined with ductoscopic imaging system is more effective.